PB2138: ORAL REGIMEN SELINEXOR, POMALIDOMIDE, AND DEXAMETHASONE IN RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (RRMM): SAFETY ASSESSMENT AND OPTIMIZATION
Authors: Juan Du, Haiyan He, Xiangqiang Fan, Lina Jin, Jing Lu, Wanting Qiang, Jin Liu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Selinexor-based regimens have demonstrated efficacy in RRMM, and selinexor is approved for treatment of relapsed/refractory MM (RRMM) in combination with either dexamethasone (Xd) or bortezomib and dexamethasone (XVd), but optimal dosing with different combination regimens remains unclear. Prior studies reported an objective response rate (ORR) of 65% and median progression-free survival (PFS) of 10.9 months with selinexor (60mg QW) combined with pomalidomide and dexamethasone (XPD-60) in RRMM patients, while XPD-40 had an ORR of 48.1%. Aims: To evaluate the effectiveness and safety of selinexor, pomalidomide, and dexamethasone in treating Chinese patients with RRMM. Methods: This is prospective, phase II study (NCT04877275) conducted in Shanghai Changzheng Hospital,China. Selinexor was administered at an initial dose of 60mg once weekly, pomalidomide at 4mg once daily on days 1-21, and dexamethasone at 40mg weekly. The dose of selinexor was later reduced to 40mg QW based on preliminary safety results and patient compliance. The primary endpoint was ORR. Results: At the data cut-off for this analysis (Feb,11,2023), 14 patients with RRMM were enrolled with a median age of 65 years (range: 50-70). The median time since initial diagnosis was 39 months and the median number of prior treatments was 2 (range: 1– 5). 85.7% of patients had ISS stage II/III disease. 57.1% of patients (8/14) had high-risk cytogenetic abnormalities, defined as one or more of del 17, t(4;14), t(14;16), or 1q amplification identified by fluorescence in situ hybridization (FISH). All 14 patients were exposed to bortezomib, 13 patients (92.9%) were refractory to lenalidomide, 11 patients (78.6%) were refractory to PIs. 10 patients (71.4%) were refractory to both PIs and LEN. For all patients, after a median treatment duration of six cycles, ORR was 64.3%. The ORR in 13 patients with lenalidomide refractory was 61.5%; 10 patients with double-refractory (ORR:50%). Initial 6 patients received XPD-60 and following 8 patients received XPD-40. ORR for XPD-60 group was 66.7%, 62.5% for XPD-40 group. Each group had one patient who achieved complete response. Common hematologic treatment-emergent adverse events (TEAEs) included (all grades: XPD-60 vs XPD-40) thrombocytopenia (66.7% vs 50%), neutropenia (50% vs 50%).Grades≥3 hematologic TEAEs were neutropenia (33.3% vs 37.5%), thrombocytopenia (16.7% vs 25%). Non-hematologic TEAEs for XPD-60 and XPD-40 were nausea (83.3% vs 25%), vomiting (16.7% vs 12.5%), fatigue (83.3% vs 50%) and infections (33.3% vs 12.5%). 4 patients in XPD-60 group experienced dose interruptions and/or dose reductions due to TEAEs and 2 patients in XPD-40 group had dose interruptions due to TEAEs Summary/Conclusion: The oral regimen selinexor in combination with pomalidomide and dexamethasone was effective in RRMM patients. But the initial 6 patients (XPD-60) experienced more frequent dose interruptions and/or dose reductions than patients in XPD -40 group and these patients mentioned that the adverse events of nausea and fatigue had an obviously bad influence on their quality of life even though they were mainly grade 1 or 2. This study suggests that XPD-40 regimen may be more feasible in clinical practice with comparable effectiveness and fewer adverse events which needs further exploration.Keywords: Imids, Multiple myeloma, relapsed/refractory